BKM120 in Esophageal Squamous Cell Carcinoma After Failure of First Line Chemotherapy

NCT01806649 | Terminated Phase 2 DMC

• 1 other identifier: 551691411
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

There is a need for more effective therapy for patients with esophageal squamous cell carcinoma who developed disease progression after first line therapy. Currently, there is no standard second-line therapy for this disease. BKM-120 is a pan-PI3K inhibitor currently tested in clinical trials. In a cellular model of oral-esophageal carcinogenesis, it has shown that EGFR overexpression activated PI3/AKT pathway. Therfore, there is interest to see the efficacy and safety of BKM120 in this setting.

Conditions

Esophageal Cancer

Keywords

esophageal cancer; second line therapy; BKM120

Outcome Measures

Primary Outcomes (1)

• disease control rate

  16-week disease control rate using RECIST 1.1 criteria

  16 weeks

Secondary Outcomes (3)

• safety

  each follow up visit, assessed up to 12 months

• progression-free survival

  Time from day 1 to date of documented disease progression or death, assessed up to 12 months

• overall survival

  Time from day 1 to date of death, assessed up to 18 months

Study Arms (1)

BKM120

EXPERIMENTAL

BKM120, starting at 100 mg oral once daily

Drug: BKM120

Interventions

BKM120 DRUG

BKM120

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided a signed Informed Consent Form (ICF) obtained prior to any screening procedure.
• Age ≥ 18 years old
• Histologically confirmed diagnosis of esophageal squamous cell carcinoma and available archival tissue for evaluation of further studies.
• Metastatic or unresectable disease
• Received one prior chemotherapy or biological therapy regimen for unresectable or metastatic disease
• More than 30 days since prior chemotherapy, surgery, radiotherapy, or investigational agents
• Measurable disease in at least 1 diameter by CT scan or MRI as per RECIST 1.1 criteria
• No evidence of brain metastasis
• ECOG ≤ 2
• Patient has adequate bone marrow and organ function
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• INR ≤ 2
• Potassium, calcium, magnesium within normal limits for the institution

You may not qualify if:

• Patient has received previous treatment with PI3K inhibitors
• Patient has symptomatic CNS metastases
• Patients with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases \> 28 days (including radiotherapy and/or surgery) prior to enrollment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
• Patient has a concurrent malignancy or has a malignancy within 5 years of study enrollment, (with the exception of nonmelanoma skin cancer or cervical carcinoma in situ.
• Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9)
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) ≥ CTCAE grade 3 anxiety
• Patient is concurrently using other approved or investigational antineoplastic agent
• Patient has had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery
• Patient has poorly controlled diabetes mellitus(HbA1c \> 8 %)
• Patient has active cardiac disease including any of the following:
• LVEF \< 50%
• QTc \> 480 msec on screening ECG (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication

Sponsors & Collaborators

• Prince of Songkla University: lead

Study Sites (1)

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Related Publications (2)

• Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012 Jan 20;30(3):282-90. doi: 10.1200/JCO.2011.36.1360. Epub 2011 Dec 12.

  PMID: 22162589 BACKGROUND

• Heeg S, Hirt N, Queisser A, Schmieg H, Thaler M, Kunert H, Quante M, Goessel G, von Werder A, Harder J, Beijersbergen R, Blum HE, Nakagawa H, Opitz OG. EGFR overexpression induces activation of telomerase via PI3K/AKT-mediated phosphorylation and transcriptional regulation through Hif1-alpha in a cellular model of oral-esophageal carcinogenesis. Cancer Sci. 2011 Feb;102(2):351-60. doi: 10.1111/j.1349-7006.2010.01796.x. Epub 2010 Dec 12.

  PMID: 21156006 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Arunee Dechaphunkul, MD

  Prince of Songkla University, Thailand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: March 7, 2013
• Study Start: July 1, 2013
• Primary Completion: April 30, 2016
• Study Completion: April 30, 2016
• Last Updated: October 11, 2021

Record last verified: 2021-10

Locations

TH (1)